A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Antiviral type III CRISPR signalling via conjugation of ATP and SAM (2023)

Chi, H., Hoikkala, V., Grüschow, S., Graham, S., Shirran, S., & White, M. F. (2023). Antiviral type III CRISPR signalling via conjugation of ATP and SAM. Nature, 622(7984), 826-833. https://doi.org/10.1038/s41586-023-06620-5

JYU-tekijät tai -toimittajat

Julkaisun tiedot

Julkaisun kaikki tekijät tai toimittajat: Chi, Haotian; Hoikkala, Ville; Grüschow, Sabine; Graham, Shirley; Shirran, Sally; White, Malcolm F.

Lehti tai sarja: Nature

ISSN: 0028-0836

eISSN: 1476-4687

Julkaisuvuosi: 2023

Ilmestymispäivä: 18.10.2023

Volyymi: 622

Lehden numero: 7984

Artikkelin sivunumerot: 826-833

Kustantaja: Nature Publishing Group

Julkaisumaa: Britannia

Julkaisun kieli: englanti

DOI: https://doi.org/10.1038/s41586-023-06620-5

Julkaisun avoin saatavuus: Avoimesti saatavilla

Julkaisukanavan avoin saatavuus: Osittain avoin julkaisukanava

Julkaisu on rinnakkaistallennettu (JYX): https://jyx.jyu.fi/handle/123456789/91239

Rinnakkaistallenteen verkko-osoite (pre-print): https://doi.org/10.1101/2023.06.26.546636

Tiivistelmä

CRISPR systems are widespread in the prokaryotic world, providing adaptive immunity against mobile genetic elements1,2. Type III CRISPR systems, with the signature gene cas10, use CRISPR RNA to detect non-self RNA, activating the enzymatic Cas10 subunit to defend the cell against mobile genetic elements either directly, via the integral histidine–aspartate (HD) nuclease domain3,4,5 or indirectly, via synthesis of cyclic oligoadenylate second messengers to activate diverse ancillary effectors6,7,8,9. A subset of type III CRISPR systems encode an uncharacterized CorA-family membrane protein and an associated NrN family phosphodiesterase that are predicted to function in antiviral defence. Here we demonstrate that the CorA-associated type III-B (Cmr) CRISPR system from Bacteroides fragilis provides immunity against mobile genetic elements when expressed in Escherichia coli. However, B. fragilis Cmr does not synthesize cyclic oligoadenylate species on activation, instead generating S-adenosyl methionine (SAM)-AMP (SAM is also known as AdoMet) by conjugating ATP to SAM via a phosphodiester bond. Once synthesized, SAM-AMP binds to the CorA effector, presumably leading to cell dormancy or death by disruption of the membrane integrity. SAM-AMP is degraded by CRISPR-associated phosphodiesterases or a SAM-AMP lyase, potentially providing an ‘off switch’ analogous to cyclic oligoadenylate-specific ring nucleases10. SAM-AMP thus represents a new class of second messenger for antiviral signalling, which may function in different roles in diverse cellular contexts.

YSO-asiasanat: bakteerit; bakteriofagit; RNA; virukset

Vapaat asiasanat: bacteria; bacteriophages; enzyme mechanisms; RNA

Liittyvät organisaatiot

OKM-raportointi: Kyllä

VIRTA-lähetysvuosi: 2023

JUFO-taso: 3